This invention relates to a pharmaceutical composition for the treatment and/or prophylaxis of mucosal damage in a mammal. In particular, this invention relates to pharmaceutical compositions including water soluble salts of alginic acid.
The gastrointestinal (GI) tract in mammals consists of the oral cavity, the esophagus, the stomach and the small and large intestines. The tract is lined by a layer of cells known as the mucosa, which is stratified squamous non-keratinized epithelium in the case of the oral cavity and the esophagus and is columnar epithelium in the case of the stomach and intestines. This mucosa suffers a number of assaults from time to time, including:                mechanical damage and/or hot/cold stress from food and drink;        exposure to contents from the stomach and duodenum (reflux); and/or        systemically and/or topically induced mucosal damage such as that caused by the action of prostaglandin inhibitors (aspirin) or indomethacin.        
All of the above (but particularly reflux) can result in local injury to the mucosa which itself can lead to esophagitis (mucosal inflammation) and, in severe or chronic instances, Barrett's esophagus (in which a lower portion of the esophagus becomes lined with columnar epithelium).
The upper GI tract has many defense mechanisms which act to counter the assaults mentioned above. These include:                the secretion of mucus and bicarbonate which are generally considered to have both a protective and a neutralizing function;        the secretion of saliva which acts to lubricate the esophagus and raise the pH in the oral cavity and esophagus;        the lower esophageal or cardiac sphincter which acts to confine gastric contents to the stomach; and        peristalsis or clearance whereby, through the action of swallowing, the bolus is moved through the esophagus to the stomach by peristaltic waves.        
Often, however, these defenses prove inadequate and damage to the mucosa or cellular lining of the oral cavity, esophagus and/or stomach occurs. This damage is characterized by injury to the upper cell layers in the mucosa.
GB-A-2324725 discloses a pharmaceutical composition suitable for forming a mucoadhesive lining in the gastrointestinal tract which comprises an alginate or alginic acid having a mannuronic acid to guluronic acid residue ratio (M/G) of at least 1. The compositions disclosed comprise a combination of a low viscosity low molecular weight alginate and a high viscosity high molecular weight alginate.
GB-A-2324724 discloses a pharmaceutical composition comprising high concentrations (e.g. 8 to 15% w/w) of sodium alginate having an M/G ratio of at least 0.6:1.
EP-A-0059221 discloses a composition for the protection of the gastrointestinal tract which comprises a water soluble salt of alginic acid. The water soluble salt has a molecular weight of 60,000 to 250,000.
WO 91/11205 discloses a method of treating wounds comprising applying to a wound a biopolymer composition comprising at least 70% molar β-D-mannuronate. The specification proposes that the alginate biopolymers may be made into fibers and spun, woven, mixed or otherwise incorporated into wound dressings. For internal wounds, such as ulcers, the biopolymer is provided as a solution that will coat the walls of the gastrointestinal tract.
However, a need still exists for a pharmaceutical composition for use in the healing of mucosal damage in a mammal.
A further need exists for the manufacture of a pharmaceutical composition which provides for the healing of mucosal damage in a mammal.